title: Preventive effect of specific antioxidant on oxidative renal cell injury associated with renal crystal formation.
abstract: OBJECTIVE
  To investigate whether calcium oxalate monohydrate (COM), a key element of hyperoxaluria, would induce renal cell injury through oxidative stress and also whether certain antioxidants could prevent chemically induced renal crystal formation in rats.
  
  
  METHODS
  COM-exerted oxidative stress on the kidney epithelial Madin-Darby canine kidney cells was assessed using the lipid peroxidation assay. Glyoxalase I (Gly-I) activity was also determined. Two antioxidants, vitamin C and N-acetylcysteine (NAC), were then tested to determine whether they could abolish such oxidative stress in Madin-Darby canine kidney cells. Both antioxidants were also tested to determine whether they might prevent or reduce renal crystal formation induced with ethylene glycol (EG) and vitamin D3 (VD3) in Wistar rats.
  
  
  RESULTS
  COM (200 μg/mL) demonstrated ∼1.3-fold greater oxidative stress with a significant reduction in cell viability and Gly-I activity compared with controls. However, such adverse events were almost completely prevented with NAC but not with vitamin C. In the animal study, no renal crystals were seen in the sham group. However, numerous crystals, with reduced Gly-I activity and elevated oxidative stress, were found in the EG-VD3 group. However, markedly (>70%) fewer crystals, with full Gly-I activity and diminished oxidative stress, were detected in the EG-VD3+NAC group.
  
  
  CONCLUSIONS
  COM exerted oxidative stress on Madin-Darby canine kidney cells, leading to cell viability reduction and Gly-I inactivation, with NAC fully preventing such adverse consequences. Similarly, numerous crystals with Gly-I inactivation and elevated oxidative stress seen in the rats (EG-VD3) were also significantly prevented with NAC supplement. Thus, NAC might have clinical implications in preventing oxidative renal cell injury and, ultimately, kidney stone formation.
authors.affiliation: Department of Urology, New York Medical College, Valhalla, NY, USA.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Fishman
authors.forename: David
authors.initials: D
authors.lastname: Green
authors.forename: Alexandria
authors.initials: A
authors.lastname: Lynch
authors.forename: Muhammad
authors.initials: M
authors.lastname: Choudhury
authors.forename: Majid
authors.initials: M
authors.lastname: Eshghi
authors.forename: Sensuke
authors.initials: S
authors.lastname: Konno
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002129:Calcium Oxalate / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology; D003460:Crystallization; D004285:Dogs; D019855:Ethylene Glycol / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology / Q000473:pathology*; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D002762:Cholecalciferol; D002129:Calcium Oxalate; D007791:Lactoylglutathione Lyase; D019855:Ethylene Glycol; D001205:Ascorbic Acid; D000111:Acetylcysteine